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REVEAL Biomarkers of Engraftment After Alternative Donor HSCT

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ClinicalTrials.gov Identifier: NCT03541889
Recruitment Status : Recruiting
First Posted : May 31, 2018
Last Update Posted : February 16, 2021
Sponsor:
Collaborators:
University of Michigan
Emory University
Information provided by (Responsible Party):
University of Oklahoma

Study Description
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Brief Summary:
The purpose of this study is to find new tests that could help determine if the newly infused bone marrow cells are growing well after bone marrow transplantation or if new bone marrow cells are needed. In this study we will use FLT imaging which is an investigational imaging test, and collect blood samples to investigate if the cells are growing well.

Condition or disease Intervention/treatment Phase
Primary Graft Failure Drug: FLT imaging and TK1 blood measurements Phase 1

Detailed Description:

This is a prospective pilot study whose primary aim is to determine whether investigational FLT imaging can detect and distinguish non-engraftment from delayed engraftment after hematopoietic stem cell transplantation (HSCT) in populations at highest risk for graft failure. The investigators will enroll 50 patients undergoing myeloblative transplantation on this trial (15 pediatric and adult recipients of cord blood stem cells, 15 pediatric and adult recipients of haplo-identical HSCT, and 20 recipients of these two stem cell sources who have not engrafted by day 28). The planned length of this trial is 5 years and it will be conducted at 3 centers: Emory/Children's Healthcare of Atlanta (pediatric and adult), University of Oklahoma (adult), and University of Michigan (pediatric and adult).

For all pediatric and adult patients undergoing cord blood HSCT, three FLT images will be taken: first, one day prior to HSCT and second and third, on days 9 and 28 after HSCT. For recipients of haplo-HSCT, the FLT images will be taken one day prior to HSCT and then on days 5 and 28 after HSCT. Pediatric and adult patients who have not engrafted by day 24 after cord or haplo-identical HSCT will undergo a single FLT PET/CT image within one week, to determine if this scan can identify graft failure versus delayed engraftment. Blood samples will also be collected from all patients for blood biomarker analysis, including thymidine kinase-1 (TK1). Each patient will be in this study for one year.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Multi-institutional Prospective Pilot Research of Imaging and Blood Biomarker EValuation of Engraftment After ALlogeneic Hematopoietic Stem Cell Transplantation
Actual Study Start Date : February 5, 2021
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : May 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cord and haplo imaging cohort
For all pediatric and adult patients undergoing cord blood HSCT, FLT PET/CT imaging will occur one day prior to HSCT and on days 9 and 28 after HSCT. For recipients of haplo-HSCT, FLT PET/CT imaging will occur one day prior to HSCT and on days 5 and 28 after HSCT.
 Drug: FLT imaging and TK1 blood measurements
F18 labeled thymidine PET/CT scans will be performed. Serum measurements of TK1 will be obtained.
Experimental: Nonengrafted cohort
Pediatric and adult patients who have not engrafted by day 24 after cord or haplo-identical HSCT will undergo a single FLT PET/CT image within one week to determine if this scan can identify graft failure versus delayed engraftment.
 Drug: FLT imaging and TK1 blood measurements
F18 labeled thymidine PET/CT scans will be performed. Serum measurements of TK1 will be obtained.


Outcome Measures
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Primary Outcome Measures :
  1. FLT SUV identifies graft failure [ Time Frame: 24-28 days ]
    To calculate if SUV > 1.2 identifies subclinical engraftment using FLT PET/CT imaging for recipients of cord and haplo-HSCT who have not engrafted within 24 days of HSCT.


Secondary Outcome Measures :
  1. Map subclinical engraftment in alternative donor HSCT [ Time Frame: Day -1 to Day 28 after HSCT ]
    Use SUV increase in particular medullary spaces to identify the first site of marrow settling after HSCT in alternative donor HSCT

  2. TK1 serum levels identify graft failure [ Time Frame: 24-28 days ]
    Calculate if TK1 level increases correlate with clinical engraftment

  3. Number of patients with CTCAE version 5 events exceeding grade 3 that are possibly, probably, or definitely attributed to the FLT imaging [ Time Frame: Day -1 to Day 28 after HSCT ]
    Safety of FLT in alternative donor HSCT - Calculate the number of patients with CTCAE version 5 events exceeding grade 3 that are possibly, probably, or definitely attributed to the FLT imaging

  4. Other cytokine and chemokine markers of graft failure [ Time Frame: 24-28 days ]
    Explore other cellular, cytokine, and chemokine markers of subclinical engraftment


Eligibility Criteria
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Ages Eligible for Study:   4 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • General

    • 4 to 60 years of age
    • Able to perform FLT imaging without anesthesia
    • Diagnosed with a condition for which myeloablative hematopoietic stem cell transplantation (HSCT) is standard of care and HSCT is planned or has occured.
    • In morphologic remission prior to HSCT
    • Patient or guardian able to give informed consent
    • No investigational therapies within past 28 days Karnofsky or Lansky performance status >60%

Arm A

  • Cord blood recipients: Absence of donor specific antibodies (DSA) to cord HLA
  • Haplo-identical recipients: > 5/10 and < 7/8 allele mismatch related donor
  • Total bilirubin < 2.5 mg/dL (unless documented Gilbert's syndrome) and transaminases < 5 x the upper limit of normal
  • Creatinine clearance or GFR > 60 ml/min/1.73 m2 (performed pre-HSCT)
  • FEV1 > 80% post-bronchodilator and DLCO Adj > 70% (performed pre-HSCT if age appropriate) and SA02 > 94% on room air
  • Ejection fraction > 50% (performed pre-HSCT)

Arm B

*Non-engraftment recipients of cord or haplo-identical HSCT: Primary graft failure as defined by ANC not > 500 for 3 consecutive days and at least 24 days after HSCT

Inclusion Criteria - Donors

Arms A and B

  • 2 cords and ≥ 4/6 match to recipient for each (as per current National Marrow Donor guidelines), with a dose ≥ 2 x 10e6 CD34 cells/kg for each cord OR > 5/10 and < 7/8 allele mismatch related donor
  • Institutional guidelines met for donor suitability

Exclusion Criteria:

  • History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent
  • Clinically significant systemic illness with manifestations of significant organ dysfunction which, in the judgment of the PI or Co-I, would render the patient unlikely to tolerate the protocol therapy or complete the study
  • Presence of active malignancy from an organ system other than hematopoietic
  • Pregnant or lactating females
  • Patients who are unable or unwilling to use effective form(s) of contraception during the course of the study
  • Prior history of fluorothymidine allergy or intolerance
  • Decline enrollment on CIBMTR research protocol
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03541889


Contacts
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Contact: Kirsten M Williams, MD 404-727-4253 kirsten.marie.williams@emory.edu
Contact: Jennifer Holter, MD Jennifer-Holter@ouhsc.edu

Locations
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United States, Georgia
Emory University Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Kirsten M Williams, MD       kirsten.marie.williams@emory.edu   
Principal Investigator: Kirsten M Williams, MD         
United States, Michigan
University of Michigan Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Gregory A Yanick, MD         
Principal Investigator: Gregory A Yanick, MD         
United States, Oklahoma
Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Jennifer Holter, MD    405-271-8777    Jennifer-Holter@ouhsc.edu   
Contact: IIT Office       SCC-IIT-Office@ouhsc.edu   
Principal Investigator: Jennifer Holter, MD         
Sponsors and Collaborators
University of Oklahoma
University of Michigan
Emory University
Investigators
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Principal Investigator: Kirsten Williams, MD Emory University
More Information
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Responsible Party: University of Oklahoma
ClinicalTrials.gov Identifier: NCT03541889    
Other Study ID Numbers: OU-SCC-REVEAL
First Posted: May 31, 2018    Key Record Dates
Last Update Posted: February 16, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No